Sterilization Posits Biomanufacturing Next Scaling Challenge

Biomanufacturing, a field that has consistently pushed the boundaries of biology, may soon be constrained by a less glamorous challenge: sterilization. Steam-in-place systems have been the conventional method for maintaining sterility in bioprocessing equipment, but these systems are costly and complex to implement. Large installations demand extensive piping networks, boilers, and specialized reactor vessels, making them a significant cost factor and a bottleneck for biomanufacturing capacity.

The shift towards disposable, single-use bioreactors has helped alleviate some of the pressure, but their economics are not easily applicable to industrial biotechnology, where production volumes are significantly higher and margins are thinner. As a result, industrial producers often continue to rely on traditional steam-based infrastructure.

Arye Lipman, COO and co-founder of Biosphere, points out that the industrial sector has largely been neglected by biopharma equipment vendors, leading to the need for custom systems built around outdated methods.

The consequences extend beyond equipment expenses. Complex aseptic systems require more time for design, construction, validation, and commissioning. Maintaining sterile conditions at a commercial scale also remains a persistent operational issue, which hinders the full potential of advances in strain engineering. This dilemma is prompting a renewed interest in alternative sterilization technologies, such as ultraviolet radiation, vaporized hydrogen peroxide, chlorine-dioxide gas, ozone, and supercritical carbon dioxide.

While each of these methods has its unique engineering trade-offs, they all aim to reduce reliance on the extensive steam infrastructure typically required for aseptic operations.

Biosphere, for instance, is exploring a reactor design that utilizes UV radiation for sterilization. This system aims to minimize steam piping and boiler requirements while reducing the energy needed for fluid sterilization. If these alternative approaches can prove reliable at an industrial scale, they could potentially alter the economics of biomanufacturing plant construction.

Facilities that require less supporting infrastructure might be built more quickly and at a lower capital cost. This development could be particularly significant as the United States seeks to bolster its domestic biomanufacturing capacity. Reduced capital requirements could also influence how manufacturers manage technology risk, potentially allowing them to distribute investments across smaller plants and expand successful processes over time.

However, transitioning away from steam will not be a simple task. Alternative sterilization methods must demonstrate consistent performance from bench scale to commercial operation. They must also seamlessly integrate with downstream purification and other unit operations while offering economics compelling enough to warrant replacing well-established equipment.

Arye Lipman notes that the chemicals industry is typically resistant to new technologies, which means that the next breakthrough in biomanufacturing may not rely solely on improvements in biological organisms. Instead, the expansion of the bioeconomy could hinge significantly on redesigning the infrastructure that supports it, including a reevaluation of sterilization practices that have been in use for generations.